Discovery of non-peptide inhibitors of Plasmepsin II by structure-based virtual screening.

Abstract

Plasmepsin II (PM II) is an attractive target for anti-malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PM II from two chemical database. Five novel non-peptide inhibitors were identified and revealed moderate inhibitory potencies with IC50 ranged from 4.62 ± 0.39 to 9.47 ± 0.71 μM. The detailed analysis of binding modes using docking simulations for five inhibitors showed that the inhibitors could be stabilized by forming multiple hydrogen bonds with catalytic residues (Asp 34 and Asp 214) and also with other key residues.

• Authors: Yuwei Song, Huangtao Jin, Xiaofeng Liu, Lili Zhu, Jin Huang, Honglin Li
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 7 Pg. 2078-82 (Apr 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23466235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Protozoan Proteins
• Aspartic Acid Endopeptidases
• plasmepsin II

Topics

• Aspartic Acid Endopeptidases (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Drug Discovery
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Models, Molecular
• Molecular Structure
• Protozoan Proteins (antagonists & inhibitors, metabolism)
• Structure-Activity Relationship